Systemic Anticancer Therapy and Thromboembolic Outcomes in Hospitalized Patients With Cancer and COVID-19
Authors: Shuchi Gulati, Chih-Yuan Hsu, Surbhi Shah, Pankil K. Shah, Rebecca Zon, Susan Alsamarai, Joy Awosika, Ziad El-Bakouny, Babar Bashir, Alicia Beeghly, Stephanie Berg, Daniel de-la-Rosa-Martinez, Deborah B. Doroshow, Pamela C. Egan, Joshua Fein, Daniel B. Flora, Christopher R. Friese, Ariel Fromowitz, Elizabeth A. Griffiths, Clara Hwang, Chinmay Jani, Monika Joshi, Hina Khan, Elizabeth J. Klein, Natalie Knox Heater, Vadim S. Koshkin, Daniel H. Kwon, Chris Labaki, Tahir Latif, Rana R. McKay, Gayathri Nagaraj, Elizabeth S. Nakasone, Taylor Nonato, Hyma V. Polimera, Matthew Puc, Pedram Razavi, Erika Ruiz-Garcia, Renee Maria Saliby, Aditi Shastri, Sunny R. K. Singh, Vicky Tagalakis, Diana Vilar-Compte, Lisa B. Weissmann, Cy R. Wilkins, Trisha M. Wise-Draper, Michael T. Wotman, James J. Yoon, Sanjay Mishra, Petros Grivas, Yu Shyr, Jeremy L. Warner, Jean M. Connors, Dimpy P. Shah, Rachel P. Rosovsky, Rikin Gandhi, Benjamin A. Gartrell, Sanjay Goel, Balazs Halmos, Della F. Makower, Darciann O' Sullivan, Nitin Ohri, R. Alejandro Sica, Amit K. Verma, Omar Butt, Mark A. Fiala, Jeffrey P. Henderson, Ryan S. Monahan, Keith E. Stockerl-Goldstein, Alice Y. Zhou, Jacob D. Bitran, Sigrun Hallmeyer, Daniel Mundt, Sasirekha Pandravada, Philip V. Papaioannou, Mauli Patel, Mitrianna Streckfuss, Eyob Tadesse, Michael A. Thompson, Philip E. Lammers, Jonathan M. Loree, Irene S. Yu, Poorva Bindal, Barbara Lam, Mary Linton B. Peters, Andrew J. Piper-Vallillo, Panos Arvanitis, Pamela C. Egan, Dimitrios Farmakiotis, Adam J. Olszewski, Kendra Vieira, Anne H. Angevine, Michael H. Bar, Salvatore A. Del Prete, Maryann Z. Fiebach, Anthony P. Gulati, Edward Hatton, Kaly Houston, Suzanne J. Rose, K. M. Steve Lo, Jamie Stratton, Paul L. Weinstein, Jorge A. Garcia, Bertrand Routy, Irma Hoyo-Ulloa, Shilpa Gupta, Amanda Nizam, Nathan A. Pennell, Nima Sharifi, Claire Hoppenot, Ang Li, Danielle S. Bitterman, Toni K. Choueiri, Jean M. Connors, George D. Demetri, Talal El Zarif, Narjust Florez, Dory A. Freeman, Antonio Giordano, Alicia K. Morgans, Anju Nohria, Sara M. Tolaney, Eliezer M. Van Allen, Wenxin Vincent Xu, Susan Halabi, Tian Zhang, Hannah Dzimitrowicz, John C. Leighton, Jerome J. Graber, Jessica E. Hawley, Elizabeth T. Loggers, Gary H. Lyman, Ryan C. Lynch, Andrew J. Portuguese, Michael T. Schweizer, Christopher T. Su, Lisa Tachiki, Shaveta Vinayak, Michael J. Wagner, Albert Yeh, Yvonne Dansoa, Na Tosha N. Gatson, Mina Makary, Jesse J. Manikowski, Joseph Vadakara, Kristena Yossef, Jennifer Beckerman, Sharad Goyal, Ian Messing, Destie Provenzano, Yuan James Rao, Lori J. Rosenstein, Dawn R. Steffes, Jessica M. Clement, Jonathan A. Cosin, Ahmad Daher, Mark E. Dailey, Rawad Elias, Omar E. Eton, Wylie Hosmer, Emily Hsu, Asha Jayaraj, Jeff Mather, Alvaro G. Menendez, Rajani Nadkarni, Oscar K. Serrano, Peter Paul Yu, Shirish M. Gadgeel, Sheela Tejwani, Melissa K. Accordino, Divaya Bhutani, Brianne E. Bodin, Dawn L. Hershman, Matthew Ingham, Shaheer A. Khan, Cynthia Masson, Gary K. Schwartz, Mariam Alexander, Sara Matar, Daniel Y. Reuben, Eric H. Bernicker, John F. Deeken, Kelly J. Jeffords, Danielle Shafer, Ana I. Cárdenas-Delgado, Rogelio Cuervo Campos, Daniel De-la-Rosa-Martinez, Ana Ramirez, Nadia Melissa Valdez-Reyes, David M. Gill, Mark A. Lewis, Clarke A. Low, Terence D. Rhodes, Michelle M. Jones, Abdul-Hai Mansoor, Sandeep H. Mashru, Mica A. Werner, Aaron M. Cohen, Brandon M. Hayes-Lattin, Shannon McWeeney, Eneida R. Nemecek, Staci P. Williamson, Grant C. Lewis, Stephanie J. Smith, Mojtaba Akhtari, Dan R. Castillo, Kimberly Cortez, Kyu Park, Mark E. Reeves, Stephanie Berg, Timothy E. O'Connor, Jessica Altman, Michael Gurley, Mary F. Mulcahy, Firas H. Wehbe, Eric B. Durbin, Amit A. Kulkarni, Heather H. Nelson, Vidhyalakshmi Ramesh, Zohar Sachs, Grace Wilson, Aditya Bardia, Genevieve Boland, Justin F. Gainor, Jeffrey Peppercorn, Kerry L. Reynolds, Leyre Zubiri, Jian Li Campian, Katherine E. Smith, Tanios S. Bekaii-Saab, Aakash Desai, Thorvardur R. Halfdanarson, Michael J. Joyner, Irbaz B. Riaz, Jonathon W. Senefeld, Colt Williams, Mark Bonnen, Daruka Mahadevan, Amelie G. Ramirez, Mary Salazar, Chen-Pin Wang, Ruben A. Mesa, Nathaniel Bouganim, Arielle Elkrief, Feras Moria, Justin Panasci, Jesse Papenburg, Donald C. Vinh, Rahul Nanchal, Harpreet Singh, Nadia Bahadur, Ting Bao, Puja H. Nambiar, Roisin E. O’Cearbhaill, Esperanza B. Papadopoulos, John Philip, Gregory J. Riely, Mark Robson, Jonathan E. Rosenberg, Adam J. Schoenfeld, Rulla Tamimi, Kim Cerrone, Jennifer Dill, Bryan A. Faller, Archana Ajmera, Sharon S. Brouha, Sharon Choi, Albert Hsiao, Erin G. Reid, Padmanabh S. Bhatt, Melissa G. Mariano, Carey C. Thomson, Mary (Grace) Glace, Jeanna L. Knoble, Cameron Rink, Rosemary Zacks, Sibel H. Blau, CarrieAnn Brown, Swathi Namburi, Lauren D. Pomerantz, Marc A. Rovito, Pragati E. Advani, Tara Cronin, Bridget Fleissner, Shipra Goel, Dharmesh Gopalakrishnan, Francisco Hernandez-Ilizaliturri, Prantesh Jain, Ariffa Kariapper, Ellis Levine, Melissa Moffitt, Tracey L. O'Connor, Igor Puzanov, Laurie J. Smith, Camille P. Wicher, Emese Zsiros, Salma K. Jabbour, Christian F. Misdary, Mansi R. Shah, Gerald Batist, Erin Cook, Khashayar Esfahani, Cristiano Ferrario, Susie Lau, Kim Ma, Wilson H. Miller, Lawrence Rudski, Miriam Santos Dutra, Machelle Wilchesky, Sana Z. Mahmood, Christopher McNair, Vasil Mico, Andrea Verghese Rivera, Becky Dixon, Hannah Heilman, Barbara B. Logan, Chaitanya Mandapakala, Elwyn C. Cabebe, Michael J. Glover, Alokkumar Jha, Ali Raza Khaki, Seema Nagpal, Lidia Schapira, Sumit A. Shah, Julie Tsu-Yu Wu, Suki Subbiah, David Whaley, Gilberto de Lima Lopes, Karen de Cardenas, Karen Russell, Brittany Stith, Sharona Taylor, Justin F. Klamerus, Sanjay G. Revankar, Daniel Addison, James L. Chen, Margaret E. Gatti-Mays, Sachin R. Jhawar, Joshua D. Palmer, Clement Pillainayagam, Daniel G. Stover, Sarah Wall, Nicole O. Williams, Saqib Hussen Abbasi, Sandy Annis, Steven Greenland, Regina Jones, Anup Kasi, Crosby D. Rock, Elizabeth M. Wulff-Burchfield, Melissa Smits, Matthias Weiss, David D. Chism, Susie Owenby, Celina Ang, Matthew D. Galsky, Megan Metzger, Jeffrey Berenberg, Catherine Uyehara, Alyson Fazio, Kathryn E. Huber, Latoya N. Lashley, Mark H. Sueyoshi, Kanishka G. Patel, Jonathan W. Riess, Hala T. Borno, Eric J. Small, Sylvia Zhang, Tessa M. Andermann, Christopher E. Jensen, Samuel M. Rubinstein, William A. Wood, Syed A. Ahmad, Punita Grover, Roman Jandarov, Jordan Kharofa, Ningjing Li, Michelle Marcum, Davendra P. S. Sohal, Olga Zamulko, Maheen Abidi, Nicole B. Balmaceda, Daniel W. Bowles, Christopher L. Geiger, Merry-Jennifer Markham, Atlantis D. Russ, Haneen Saker, Jared D. Acoba, Horyun Choi, Young Soo Rho, Lawrence E. Feldman, Gerald Gantt, Kent F. Hoskins, Mahir Khan, Li C. Liu, Ryan H. Nguyen, Mary M. Pasquinelli, Candice Schwartz, Neeta K. Venepalli, Praveen Vikas, Yousef Zakharia, Anne M. Boldt, Leslie A. Fecher, Chris Su, Ragneel Bijjula, Blanche H. Mavromatis, Mildred E. Seletyn, Barbara R. Wood, Qamar U. Zaman, Virginia Kaklamani, Alaina J. Brown, Lawrence J. Charles, Alex Cheng, Marta A. Crispens, Sarah Croessmann, Elizabeth J. Davis, Tan Ding, Stephany N. Duda, Kyle T. Enriquez, Benjamin French, Erin A. Gillaspie, Daniel J. Hausrath, Cassandra Hennessy, Douglas B. Johnson, Judy T. Lewis, Xuanyi (Lexi) Li, Lauren S. Prescott, Sonya A. Reid, Sara Saif, Yu Shyr, David A. Slosky, Carmen C. Solorzano, Tianyi Sun, Lucy L. Wang, Yuanchu James Yang, David M. Aboulafia, Theresa M. Carducci, Karen J. Goldsmith, Susan Van Loon, Umit Topaloglu, Joan Moore, Wilhelmina D. Cabalona, Elizabeth Shisler, Briana Barrow McCollough, Prakash Peddi, Lane R. Rosen, Mehmet A. Bilen, Cecilia A. Castellano, Deepak Ravindranathan, Navid Hafez, Roy S. Herbst, Patricia LoRusso, Maryam B. Lustberg, Tyler Masters, Catherine Stratton, Corrie A. Painter, Solange Peters
Journal: JAMA Oncology (2023)

Importance Systematic data on the association between anticancer therapies and thromboembolic events (TEEs) in patients with COVID-19 are lacking. Objective To assess the association between anticancer therapy exposure within 3 months prior to COVID-19 and TEEs following COVID-19 diagnosis in patients with cancer. Design, Setting, and Participants This registry-based retrospective cohort study included patients who were hospitalized and had active cancer and laboratory-confirmed SARS-CoV-2 infection. Data were accrued from March 2020 to December 2021 and analyzed from December 2021 to October 2022. Exposure Treatments of interest (TOIs) (endocrine therapy, vascular endothelial growth factor inhibitors/tyrosine kinase inhibitors [VEGFis/TKIs], immunomodulators [IMiDs], immune checkpoint inhibitors [ICIs], chemotherapy) vs reference (no systemic therapy) in 3 months prior to COVID-19. Main Outcomes and Measures Main outcomes were (1) venous thromboembolism (VTE) and (2) arterial thromboembolism (ATE). Secondary outcome was severity of COVID-19 (rates of intensive care unit admission, mechanical ventilation, 30-day all-cause mortality following TEEs in TOI vs reference group) at 30-day follow-up. Results Of 4988 hospitalized patients with cancer (median [IQR] age, 69 [59-78] years; 2608 [52%] male), 1869 had received 1 or more TOIs. Incidence of VTE was higher in all TOI groups: endocrine therapy, 7%; VEGFis/TKIs, 10%; IMiDs, 8%; ICIs, 12%; and chemotherapy, 10%, compared with patients not receiving systemic therapies (6%). In multivariable log-binomial regression analyses, relative risk of VTE (adjusted risk ratio [aRR], 1.33; 95% CI, 1.04-1.69) but not ATE (aRR, 0.81; 95% CI, 0.56-1.16) was significantly higher in those exposed to all TOIs pooled together vs those with no exposure. Among individual drugs, ICIs were significantly associated with VTE (aRR, 1.45; 95% CI, 1.01-2.07). Also noted were significant associations between VTE and active and progressing cancer (aRR, 1.43; 95% CI, 1.01-2.03), history of VTE (aRR, 3.10; 95% CI, 2.38-4.04), and high-risk site of cancer (aRR, 1.42; 95% CI, 1.14-1.75). Black patients had a higher risk of TEEs (aRR, 1.24; 95% CI, 1.03-1.50) than White patients. Patients with TEEs had high intensive care unit admission (46%) and mechanical ventilation (31%) rates. Relative risk of death in patients with TEEs was higher in those exposed to TOIs vs not (aRR, 1.12; 95% CI, 0.91-1.38) and was significantly associated with poor performance status (aRR, 1.77; 95% CI, 1.30-2.40) and active/progressing cancer (aRR, 1.55; 95% CI, 1.13-2.13). Conclusions and Relevance In this cohort study, relative risk of developing VTE was high among patients receiving TOIs and varied by the type of therapy, underlying risk factors, and demographics, such as race and ethnicity. These findings highlight the need for close monitoring and perhaps personalized thromboprophylaxis to prevent morbidity and mortality associated with COVID-19–related thromboembolism in patients with cancer.